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Background: The UVB and heat rekindling (UVB/HR) model shows potential as a translatable inflammatory pain model. However, the occurrence of central sensitization in this model, a fundamental mechanism underlying chronic pain, has been debated. Face, construct and predictive validity are key requisites of animal models; electromyogram (EMG) recordings were utilized to objectively demonstrate validity of the rat UVB/HR model. Methods: The UVB/HR model was induced on the heel of the hind paw under anaesthesia. Mechanical withdrawal thresholds (MWTs) were obtained from biceps femoris EMG responses to a gradually increasing pinch at the mid hind paw region under alfaxalone anaesthesia, 96 h after UVB irradiation. MWT was compared between UVB/HR and SHAM‐treated rats (anaesthetic only). Underlying central mechanisms in the model were pharmacologically validated by MWT measurement following intrathecal N‐methyl‐d‐aspartate (NMDA) receptor antagonist, MK‐801, or saline. Results: Secondary hyperalgesia was confirmed by a significantly lower pre‐drug MWT {mean [±standard error of the mean (SEM)]} in UVB/HR [56.3 (±2.1) g/mm2, n = 15] compared with SHAM‐treated rats [69.3 (±2.9) g/mm2, n = 8], confirming face validity of the model. Predictive validity was demonstrated by the attenuation of secondary hyperalgesia by MK‐801, where mean (±SEM) MWT was significantly higher [77.2 (±5.9) g/mm2n = 7] in comparison with pre‐drug [57.8 (±3.5) g/mm2n = 7] and saline [57.0 (±3.2) g/mm2n = 8] at peak drug effect. The occurrence of central sensitization confirmed construct validity of the UVB/HR model. Conclusions: This study used objective outcome measures of secondary hyperalgesia to validate the rat UVB/HR model as a translational model of inflammatory pain. [ABSTRACT FROM AUTHOR]

The paths that link the periaqueductal grey (PAG) to hindbrain motor circuits underlying changes in behavioural responsiveness to external stimuli are unknown. A major candidate structure for mediating these effects is the cerebellum. The present experiments test this directly by monitoring changes in size of cerebellar responses evoked by peripheral stimuli following activation of the PAG. In 22 anaesthetized adult Wistar rats, climbing fibre field potentials were recorded from the C1 zone in the paramedian lobule and the copula pyramidis of the cerebellar cortex evoked, respectively, by electrical stimulation of the ipsilateral fore- and hindlimb. An initial and a late response were attributable to activation of Abeta and Adelta peripheral afferents respectively (hindlimb onset latencies 16.9 and 23.8 ms). Chemical stimulation at physiologically-identified sites in the ventrolateral PAG (a region known to be associated with hyporeactive immobility) resulted in a significant reduction in size of both the Abeta and Adelta evoked field potentials (mean reduction relative to control +/- SEM, 59 +/- 7.5 and 66 +/- 11.9% respectively). Responses evoked by electrical stimulation of the dorsal or ventral funiculus of the spinal cord were also reduced by PAG stimulation, suggesting that part of the modulation may occur at supraspinal sites (including at the level of the inferior olive). Overall, the results provide novel evidence of descending control into motor control centres, and provide the basis for future studies into the role of the PAG in regulating motor activity in different behavioural states and in chronic pain.

The periaqueductal grey can differentially control A- vs. C-nociceptor-evoked spinal reflexes and deep spinal dorsal horn neuronal responses. However, little is known about the control of A- vs. C-fibre inputs to lamina I and the lateral spinal nucleus, and how this correlates with the control of deeper laminae. To address this, the laminar distributions of neurones expressing Fos-like immunoreactivity were determined following preferential activation of A- or C-heat nociceptors, using fast or slow rates of skin heating, respectively, in the absence or presence of descending control evoked from the periaqueductal grey. In lamina I, numbers of Fos-positive neurones following both fast and slow rates of skin heating were reduced significantly following activation in the ventrolateral and dorsolateral/lateral periaqueductal grey. In contrast, in the deep dorsal horn (laminae III-VI), activation in both the ventrolateral and dorsolateral/lateral periaqueductal grey significantly reduced the numbers of Fos-positive neurones evoked by C- but not A-nociceptor stimulation. C- but not A-heat nociceptor activation evoked Fos bilaterally in the lateral spinal nucleus. Stimulation in the ventrolateral but not the dorsolateral/lateral periaqueductal grey significantly increased the numbers of Fos-positive neurones evoked by A- and C-nociceptor stimulation bilaterally in the lateral spinal nucleus. These data have demonstrated differences in the descending control of the superficial vs. the deep dorsal horn and lateral spinal nucleus with respect to the processing of A- and C-fibre-evoked events. The data are discussed in relation to the roles of A- and C-nociceptors in acute and chronic pain.